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C N Scholfield

Publications and source records attributed to C N Scholfield.

At least 19 recordsLinked to original sources
PubMed1992

Phorbol ester and lignocaine or pentobarbitone interactions at presynaptic axons.

The interaction between anaesthetics and protein kinase C activation was studied in unclamped field currents from unmyelinated axons which give rise to en passant synapses. Electrical responses could be resolved into Na, K and Ca components revealed by electrode polarisation pretreatment with blockers of K-conductances. In the presence of phorbol dibutyrate, there was an increase in the potency of lignocaine, pentobarbitone and tetrodotoxin: for the Na current, the potency increased by 2.67 +/- 0.64, 2.35 and 2.47 fold respectively. The potentiation does not appear to be any indirect result of changed membrane potential. It is suggested that protein kinase C phosphorylation of membrane channel proteins increases the effectiveness of these substances.

Animals↗
PubMed1991

Action of general anaesthetics on unclamped Ca(2+)-mediated currents in unmyelinated axons of rat olfactory cortex.

Na+ and Ca2+ currents were monitored using a suction electrode in unclamped presynaptic axons of rat olfactory cortex pretreated with 0.1 mM 3,4-diaminopyridine and 5 mM tetraethylammonium. The effects of anaesthetics on these currents were compared with tetrodotoxin or cadmium. Ketamine (0.1-1 mM), ether (20-200 mM), diisopropylphenol (0.01-0.5 mM) and lignocaine (0.01-0.2 mmol/l) all depressed both the initial Na+ component and the Ca(2+)-mediated tail of the response. Urethane (5-100 mM), halothane (1-5 mM) and pentobarbitone (0.1-2 mM) showed slight selectivity for the axonal Ca2+ tail. Diisopropylphenol apparently enhanced the Ca2+ tail at low concentrations. The alphaxalone (1-50 microM) depression was very weak. In a few cases the depression may contribute to anaesthesia but with others, high concentrations may contribute to the toxicity of the substances in vivo.

Anesthetics↗
PubMed1991

Interaction between phorbol dibutyrate and anaesthetics on synaptic responses from olfactory cortex of rat.

Phorbol esters have been shown to enhance the release of transmitters and to potentiate the effect of local anaesthetics in olfactory cortex of the rat. This work examined the interaction between phorbol dibutyrate and a range of substances, which act on axonal conduction and synaptic transmission. Synaptically-evoked field responses were elicited by stimulation of the lateral olfactory tract of slices of olfactory cortex, maintained in vitro. Ketamine (0.2-1.0 mM), benzocaine (0.2-1 mM), atropine (0.1-2 mM) and tetrodotoxin (20-200 nM) depressed synaptic transmission and, in the presence of phorbol dibutyrate (1 microM), these substances were more potent by 3.7 +/- 0.5, 1.5 +/- 4, 2.6 +/- 0.6 and 5.5 +/- 1.8 fold, respectively. Pentobarbitone (0.1-2.0 mM) with or without bicuculline, urethane (10-200 mM), halothane (0.5-5.0 mM) (with bicuculline) and ethanol (50-500 mM) also depressed synaptic transmission but their effectiveness was not potentiated by phorbol dibutyrate. It is thought that the increased potency, produced by phorbol ester, was associated with a presynaptic action of those substances.

Anesthetics↗
PubMed1991

Phorbol dibutyrate enhances local anaesthetic action.

1. Synaptically-evoked field responses were elicited by stimulation of the lateral olfactory tract of rat olfactory cortex slices maintained in vitro. 2. Various concentrations of lignocaine (5-500 microM) were applied to the solution bathing the slices. These produced dose-dependent depressions of the synaptically-evoked potential over the concentration range 20-500 microM. The responses completely recovered on washing out the lignocaine. Similar depressions were also noted for procaine (100-1000 microM). 3. In the 47 slices tested, application of beta-phorbol 12,13-dibutyrate (1 microM) increased the amplitude of the synaptic response (from 0.99 +/- 0.05 to 1.36 +/- 0.06 mV). beta-Phorbol 13-monbutyrate (1 microM) had no effect. 4. In the presence of phorbol dibutyrate the depressant effect of lignocaine was increased: the EC50 changed from 91 +/- 10 to 24 +/- 2 microM (a mean potency increase of 3.47 +/- 0.14). A similar increase in potency for procaine was observed with phorbol dibutyrate (from 264 +/- 23 to 49 +/- 9 microM: a 5.49 +/- 0.82 increase in potency). If the tissue was pre-equilibrated in a concentration of lignocaine which produced a 60-80% depression, addition of phorbol ester caused a complete abolition of the evoked potential. 5. beta-Phorbol 13-monobutyrate (1 microM) had no effect on the potency of lignocaine. 6. The Na and K currents generating the action potential in the presynaptic nerve terminals were unaffected by phorbol dibutyrate. The depressant effect of lignocaine on these currents was not modified by phorbol dibutyrate. The depressant effect of lignocaine on these currents was not modified by phorbol dibutyrate. 7. The potentiation of lignocaine could not be accounted for by membrane depolarization or by nonspecific actions of phorbol dibutyrate, and was distinct from the action on transmitter release. Therefore, it seems likely that protein kinase C activation was responsible for the modified action of lignocaine, although the mechanism for this is unclear.

Anesthetics, Local↗
PubMed1990

Properties of K-currents in unmyelinated presynaptic axons of brain revealed revealed by extracellular polarisation.

Thin pial surface slices of guinea-pig olfactory cortex contain unmyelinated axons derived from the lateral olfactory tract (LOT). The severed ends of the groups of these axons were drawn into a suction electrode to record the currents resulting from propagated action potentials. On stimulating these unmyelinated axons, a tetrodotoxin-sensitive positive current of 22.5 +/- 3.0 nA was recorded by the suction electrode. The positive current was often followed by a small negative current. A 100 mV positive polarisation applied to the suction electrode revealed a large negative after-current (25.8 +/- 3.5 nA). In contrast, the positive current was slightly reduced by the polarisation. The early phases of the negative after-current induced by the electrode polarisation were blocked by 3,4-diaminopyridine, 4-aminopyridine or 2,3-diaminopyridine (in order of potency). The entire negative after-current was blocked by prolonged (3 h) equilibration in a medium containing 3.5 mmol/l Cs and 1.5 mmol/l K. Tetraethylammonium (TEA) or Ba2+ by themselves had little effect. In aminopyridine, the residual negative after-current was blocked by TEA (10 mmol/l) or 1 mmol/l Ba2+. Muscarinic agonists had no effect on these currents. These experiments show that some axonal currents can be revealed by extracellular polarisation and that these axons rely on an 'A' type of current for the rapid repolarisation of the membrane although slower K-channels are present.

Action Potentials↗
PubMed1990

Studies on unmyelinated axons and varicosities in the olfactory cortex.

The main afferent input to the olfactory cortex from the olfactory bulbs is via the lateral olfactory tract (LOT). The axons within the lateral olfactory tract are myelinated. On leaving the LOT, they lose their myelination as they fan out over the layer immediately beneath the pial surface to make en passant synaptic connections with dendrites from neurones within the olfactory cortex. Using the guinea-pig, a semiquantitative electron micrographical study was made of the density and dimensions of these unmyelinated axons and the varicosities they create. The unmyelinated axons were very fine (0.17 +/- 0.004 micron in diameter) and punctuated at 2 microns intervals by varicosities containing a single type of vesicle. The electrophysiological consequences of this close varicosity spacing is that axonal and varicosity membranes behave electrically as single units.

Animals↗
PubMed1990

Adenosine-induced enhanced recovery of evoked responses after anoxia.

Transverse slices of rat hippocampus were used to test the effect of adenosine on recovery of synaptically-evoked potentials after anoxia. To produce conditions better resembling ischaemia, glucose was omitted during the period of anoxia. Anoxia abolished all electrical activity within 5 min. The responses recovered completely after short periods of anoxia (3 min), but the amount of recovery was progressively reduced with longer exposures. The recovery was enhanced by the presence of 100 microM adenosine: the exposure time giving a 50% recovery of the response was 17.6 +/- 1.8 min in normal solution and 29.0 +/- 4.1 min with adenosine. These results are consistent with the idea that adenosine offers some protection from anoxia.

Adenosine↗
PubMed1990

General anaesthetics and field currents in unclamped, unmyelinated axons of rat olfactory cortex.

1. The effects of seven general anaesthetics and one local anaesthetic having a wide range of physical and chemical properties were studied on nerve terminal Na- and K-mediated currents in slices of olfactory cortex. These currents were measured from the groups of fine unmyelinated axons traversing the surface of the olfactory cortex and which give off synapses en passant. The amplitude of the K-current was visualized by depolarizing the axons via an electrode polarization. 2. The anaesthetics tested were ketamine (0.1-2 mM), pentobarbitone (0.1-5 mM), urethane (5-200 mM), halothane (0.5-5 mM), ether (10-200 mM), alphaxalone (0.001-0.05 mM), diisopropylphenol (0.05-0.5 mM) and lignocaine (0.01-0.5 mM). All had depressant effects on the axonal Na-current (at the higher concentrations tested) and on the K-current (at slightly lower concentrations). The apparent lower potency on the Na-current was considered to be due to a masking of effect as a consequence of the reduction in the K-mediated membrane rectification rather than any real difference in the susceptibilities of the Na and K-currents. 3. Some of the depressant effect of pentobarbitone and alphaxalone was gamma-aminobutyric acid (GABA)-mediated as indicated by the reduced potency in the presence of bicuculline. The actions of ketamine and halothane were unaffected by bicuculline. 4. For some anaesthetics these axonal depressant effects might contribute to general anaesthesia, while for other substances the relatively high concentrations necessary would suggest that this mode of action does not produce effective anaesthesia in vivo.

Anesthetics↗
PubMed1989

A phorbol diester-induced enhancement of synaptic transmission in olfactory cortex.

1. Extracellular field synaptic potentials were recorded from pial surface slices of guinea-pig olfactory cortex maintained in vitro. 2. Phorbol 12,13-dibutyrate (0.1-10 microM) enhanced the amplitude of the evoked potential (by 51.2 +/- 10.4% with 1 microM) in normal solution. When the evoked potential was partially depressed by Cd, Co, Mn or a reduced Ca concentration, phorbol 12,13-dibutyrate (1 microM) induced a much larger enhancement of the evoked potential (196.5 +/- 24.4% increase). Phorbol 12,13-diacetate and mezerein had similar effects but were less potent. 4 beta-Phorbol (10 microM) had no effect. 3. The diacylglycerol analogues, dioctanoylglycerol (100-1000 microM), 1-oleoyl-2-acetylglycerol (100-500 microM) or diolein (100 microM) had no effect on the evoked potentials, either alone or in the presence of Cd. 4. The isoquinolinylsulphonamide inhibitor (H-7) of protein kinase C slightly enhanced the e.p.s.p. and had no effect on the potentiation produced by phorbol ester. Another protein kinase C inhibitor, acridine orange (100-1000 microM), had no effect on the action of phorbol ester. 5. These results show that transmitter release, as at other synapses, is enhanced by phorbol esters but Ca did not potentiate this action. The pharmacological profile of the effect on transmitter release differed from that of protein kinase C in cell-free preparations and therefore it is unclear whether protein kinase C was involved in the present study.

Animals↗
PubMed1988

Presynaptic Na/Ca action potentials in unmyelinated axons of olfactory cortex.

(1) Pial surface slices of guinea-pig olfactory cortex were cut to have a thickness of 150 micron. Action potentials were recorded from the sectioned ends of the unmyelinated afferent axons originating from the lateral olfactory tract (LOT). These potentials were prolonged by the K-channel blocker 3,4-diaminopyridine (0.1 mmol/l) and further lengthened by tetraethylammonium (10 mmol/l). The action potential was also greatly prolonged by partly replacing the K+ in the bathing solution by Cs+. (2) These prolonged action potentials were shortened by Cd2+; Gd3+ (gadolinium); Ni2+; Mn2+; Co2+, in order of potency. The residual early component of the action potential was tetrodotoxin (TTX) sensitive. In contrast, the LOT action potential was little affected by Ca-channel blockade. (3) Organic Ca-channel blockers either had no effect (0.05 mmol/l nifedipine), or depressed the early and later phases of the prolonged action potential equally (0.05-0.5 mmol/l verapamil or 0.05-0.2 mmol/l diltiazem). (4) A propagated action potential was also obtained in solution containing TTX and low Na+. This potential was supported by Ca2+, Sr2+ or Ba2+ and completely suppressed by Cd2+. (5) The later parts of the action potential, after K-channel blockade, had a pharmacological sensitivity towards Ca-channel blockers matching that of synaptic transmission. This suggests the falling phase of the action potential is caused by charge carrier (mainly Ca2+) passing through Ca-channels that have similar properties to, or are the same as those which open prior to transmitter release.

4-Aminopyridine↗
PubMed1988

Presynaptic K-channel blockade counteracts the depressant effect of adenosine in olfactory cortex.

Slices of isolated olfactory cortex from guinea-pig have been used to study the action of adenosine at synapses between axons of the lateral olfactory tract and neurons in the olfactory cortex. Adenosine depressed the excitatory postsynaptic potential, and, with paired or multiple stimuli, the reduced excitatory postsynaptic potentials in adenosine showed more synaptic facilitation. Very small excitatory postsynaptic potentials which were estimated not to be affected by postsynaptic membrane conductance changes were highly sensitive to adenosine. Both observations indicate a presynaptic action of adenosine. To test whether a conductance increase to potassium ions mediated adenosine action, the K-channel blockers, 3,4-diaminopyridine (1-100 mumol/l) or 4-aminopyridine (100-500 mumol/l) were applied or Cs partially substituted for K. These substances reduced or prevented adenosine from having its depressant effect on synaptic transmission. These particular K-channel blockers also prolonged the action potential propagating along the lateral olfactory tract. When the increased excitability was counteracted by high Mg or low concentrations of tetrodotoxin, 3,4-diaminopyridine still blocked adenosine action. UO2 ions prolonged the lateral olfactory tract action potential without blockade of K-conductance, but still supported an adenosine depression of the excitatory postsynaptic potential. Veratridine also supported the adenosine depression. These observations suggest that the action of 3,4-diaminopyridine on adenosine was not solely the result of increased tissue excitability. In contrast, tetraethylammonium (20 mmol/l), Ba (0.5-4 mmol/l) or Rb replacement for K had a negligible effect on the duration of the presynaptic action potential and had no effect on the depressant action of adenosine. These data are compatible with the idea that adenosine enhances an aminopyridine-sensitive potassium conductance in nerve terminals and changes in Ca influx are consequential to this.

4-Aminopyridine↗
PubMed1987

A miniaturised roller pump.

A roller pump is described which is able to pump microlitre quantities of solution in either direction. It depends upon a caged roller bearing where the individual rollers press against silicon rubber tubing having an internal diameter of 0.5 mm. This assembly was housed in a cylindrical cavity shaped to produce a non-pulsatile flow. The pump is driven by a stepping motor to produce a constant flow rate. It is used to obtain small samples of bathing solution from near the surface of brain slices to monitor efflux of amino acids.

Equipment Design↗
PubMed1987

Pulse-modulated light source for psychometric and vision experiments.

Light-emitting diodes (LED) of various colours were used to produce accurately controllable light sources. Variable light intensity was obtained by applying 800-ns current pulses to the LEDs at frequencies 1-1000 kHz using a single potentiometer. These current pulses were generated from an oscillator which was voltage-controlled from a potentiometer and an antilogarithmic amplifier. Its output was gated to produce an optional flicker of 1-100 Hz. The light intensity was indicated by a frequency meter connected to the oscillator. The reading of this was found to linearly indicate light intensity.

Color Perception Tests↗
PubMed1986

Ca-channel blockers and the electrophysiology of synaptic transmission of the guinea-pig olfactory cortex.

Slices of guinea-pig olfactory cortex have been used to compare the potency of various Ca-blockers on the electrophysiology of synaptic transmission. Listed in the order of potency, the divalent cations Cd2+, Ni2+, Mn2+, Co2+, La3+ and Mg2+ depressed synaptic transmission. The organic Ca-blockers, nifedipine or nimodipine or verapamil and diltiazem were ineffective up to 0.01 mmol/l. Verapamil, D600 or diltiazem (0.1-0.3 mmol/l) depressed both synaptic transmission and the sodium-mediated presynaptic action potential. These results reaffirm the idea that 'organic Ca-antagonist' do not block all Ca-channels in brain and the high Cd2+ sensitivity suggests the Ca-channels in post- and presynaptic membranes have dissimilar pharmacological profiles.

Animals↗
PubMed1986

Effects of adenosine uptake blockers and adenosine on evoked potentials of guinea-pig olfactory cortex.

The olfactory cortex slice preparation from guinea-pig has been used to test compounds which inhibit the cellular uptake of adenosine. The uptake inhibitors dipyridamole (0.1-10 mumol/l), dilazep (1-10 mumol/l) nitrobenzylthioguanosine (1-10 mumol/l), nitrobenzylthioinosine (0.1-5 mumol/l), and hexobendine (1-100 mumol/l) increased the potency of adenosine (0.1-30 mumol/l) by up to 5-fold but did not potentiate cyclohexyladenosine (0.01-10 mumol/l). The benzodiazepine, diazepam (1 mumol/l) slightly increased the potency of adenosine (by 1.7-fold) whereas flurazepam (3 mumol/l) had no effect, suggesting that inhibition of adenosine uptake is probably not the major therapeutic action of these compounds. The uptake inhibitors depressed the amplitude of the monosynaptic epsp when added alone, an effect reversed by adenosine deaminase (1 unit/ml) whereas the adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine (10 mumol/l) had no effect on adenosine action. These results show that in this preparation (a) adenosine action is attenuated by an uptake mechanism and (b) endogenous adenosine release normally has no apparent effects on synaptic transmission at low stimulus rates. Nitrobenzylthioinosine and nitrobenzylthioguanosine are probably the best uptake blockers.

Adenosine↗
PubMed1985

gamma-Aminobutyric acid partly mediates the pentobarbitone depression of synaptic excitation in the guinea-pig olfactory cortex in vitro.

Pentobarbitone depresses synaptic excitation in the guinea-pig olfactory cortex slice in vitro. A study has been made to elucidate the possible role of gamma-aminobutyric acid (GABA) in this depression by testing pentobarbitone in the presence of high concentrations of the GABA blockers, i.e. picrotoxin or bicuculline. These blockers reduced the action of pentobarbitone; the dose-depression curve for pentobarbitone was shifted to the right by a factor of 2.3. It is concluded that pentobarbitone has a bimodal action, one action via GABA and another unrelated to GABA or Cl- conductances.

Animals↗